2000-08-11-14 Agenesis of the corpus callosum © Gonçalves www.thefetus.net/
Agenesis of the corpus callosum
Luis F. Gonçalves, MD - Maria Verônica Munoz Rojas, MD
Updated 08.22.2007 by F.G.
Partial or complete absence of the corpus callosum, generally affecting the posterior aspect of the structure1
30-70:10,000 for the general population and 2 to 3 % of those with mental disabilities.2-4
The corpus callosum is a white matter structure located in the midline and composed of fibers that connect both cerebral hemispheres. Complete agenesis of the corpus callosum may occur after inflammatory or vascular lesions occurring after 12 weeks. Later insults result in partial agenesis of a previously normal corpus callosum; therefore, generally only the posterior portion is affected.1
The development of the corpus callosum begins during the fifth week of fetal life with the formation of the primitive lamina terminalis, which thickens to form the commissural plate. Glial cells coalesce to form a bridge like structure that serves as a guide for the callosal fibers crossing the longitudinal cerebral fissure to their targets on the contralateral side of the brain. The mature corpus callosum is formed by the seventeenth week of gestation.5
Different mechanisms may result in agenesis of the corpus callosum (ACC). Among those, there are two forms of true ACC. In the first one, axons are formed but are incapable of crossing the middle because of the absence of "massa comissuralis"; instead, nerve fibers follow a caudal course, grouped in a thick longitudinal bundle (Probst bundle), below the cingulus and above the phornix; this bundle separates the anterior horns of the lateral ventricles and the third ventricle may be, at times, dislocated superiorly. In the second middle, ACC is caused by defects in the formation of commissural axons in the cerebral cortex.1
Diagnosis is suspected when the posterior horn of the lateral ventricle is dilated, giving the ventricle a “tear drop” aspect. The third ventricle is usually dilated and dislocated towards the interhemispheric fissure. In coronal sections, it is not possible to visualize the corpus callosum. ACC is better documented in coronal and sagittal sections of the fetal brain; therefore, it may be necessary to perform a transvaginal examination.
|Figure 1. Transverse section through the cerebral cortex demonstrating a "tear drop" shaped ventricle. Observe the relative dilation of the posterior horn of the lateral ventricle and separation of the anterior horns.
||Figure 2. Transverse section through the superior portion of the cortex of a fetus with ACC.
||Figure 3. A transverse section slightly below the one in Figure 2. The cavum septum pellucidum is not visualized.
|Figure 4. Diagram representing the sagittal section of a normal brain. The corpus callosum is represented in gray.
|| Figure 5. Diagram representing the coronal section of a normal brain. The corpus callosum is observed as a bundle of fibers crossing the midline (represented in gray).
||Figure 6. Diagram representing a transverse section of a normal brain. The corpus callosum is observed as a bundle of fibers crossing the midline (represented in gray).
Isolated agenesis of the corpus callosum may be confused with moderate hydrocephaly. In hydrocephaly, one of the clues that differentiate this disorder from ACC is the presence of the cavum septum pellucidum.
ACC may be an isolated finding; however, it is frequently associated with other malformations and genetic syndromes including chromosomal aberrations and inborn errors of metabolism.4,6-7 Associated central nervous system (CNS) abnormalities include Chiari malformations, anomalies of neuronal migration including lissencephaly, schizencephaly, pachygyria and polymicrogyria, encephaloceles, Dandy-Walker malformations, holoprosencephaly, and olivopontocerebellar degeneration.8 Extracranial malformations include abnormalities of the face and of the cardiovascular, genitourinary, gastrointestinal, respiratory, and musculoskeletal systems.6,9-11
Associated genetic syndromes
Over 175 genetic syndromes may present partial or total agenesis of the corpus callosum, with different etiologies, including inborn errors of metabolism, chromosome and Mendelian disorders. These diseases are associated with specific malformations that allow a precise differential diagnosis in the majority of the cases: Aicardi, Andermann, Acrocalosal, FG, Naiman & Fraser, Ziegler, Menkes, Dogan, Shapira & Cohen, Cao, Lynn, Kaplan, Wilson, Pineda, Young.12
Prognosis is dependent upon the cause of the malformation. In approximately 90% of the cases of isolated ACC, development is normal. ACC can even be an occasional finding in the investigation of children with mental retardation or microcephaly.11
Agenesis of the corpus callosum is one of the most common brain malformations observed in humans. It is a heterogeneous malformation, with many etiologies. The recurrence risk of ACC, whether it is isolated or in addition to inborn errors of metabolism or genetic syndromes, depends on the underlying cause. If ACC is associated with aneuploidy the recurrence risk is 1% or the maternal-age related risk for aneuploidy, whichever is greater. Isolated ACC with no known cause is usually sporadic but familial cases have been reported and the recurrence risk is probably on the order of 2 to 3%.12 ACC is a known criterion for the diagnosis of certain syndromes, such as Aicardi, Andermann, and acrocallosal syndromes. Prenatal counseling for fetal agenesis of the corpus callosum is difficult as the prognosis is uncertain. The association with other cerebral abnormalities increases the likelihood of a poor outcome but ultrasonographic assessment of the fetal brain is limited and magnetic resonance imaging evaluation might be necessary.14
There is no treatment for this condition
Support groups, parent"s & patient"s web pages
ACC Network & ACC-Listserv E-Mail Support Group
Parent"s web pages
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